Summary of findings

This case series describes three infants who developed prolonged pulmonary dysfunction after Glenn or Fontan procedures, each following an infectious episode associated with elevated inflammatory markers. All patients showed markedly increased serum KL-6 and SP-D levels, with SP-A elevated in two, consistent with diffuse alveolar–interstitial injury and type II pneumocyte activation.

Steroid therapy yielded only partial or delayed improvement, and one patient died of respiratory failure. These observations suggest that postoperative infection may precipitate a sustained inflammatory process in the context of Glenn/Fontan physiology, contributing to prolonged lung injury and elevated epithelial biomarkers.

Mechanisms of lung injury in right-heart bypass circulation

Glenn and Fontan circulations are characterised by non-pulsatile pulmonary flow, elevated venous pressure, and impaired lymphatic drainage, all of which increase endothelial stress and interstitial fluid accumulation. ^{Reference Dittrich, Weise and Cesnjevar3,Reference Zongtao, Huishan and Zengwei4} These chronic abnormalities may weaken the alveolar–capillary interface and reduce the lung’s ability to recover from inflammatory or infectious insults.

Recent longitudinal data suggest that single-ventricle patients can have persistent impairment of the alveolar–capillary membrane from fetal life through the Fontan circulation, indicating a chronic structural vulnerability. ^{Reference Ravndal, Idorn, Nielsen and Hjortdal5} Such vulnerability may amplify epithelial injury and biomarker leakage once acute respiratory distress syndrome develops, potentially explaining the unusually high KL-6 and surfactant protein levels observed in our cases.

Differential diagnosis: Acute respiratory distress syndrome vs. Interstitial pneumonia

In all three cases, preoperative pulmonary vascular resistance and ventricular function were favourable, and the Glenn/Fontan circulation remained stable, indicating that infection rather than circulatory failure triggered the lung injury. All patients met paediatric acute respiratory distress syndrome criteria, including acute onset and bilateral non-cardiogenic infiltrates; However, oxygenation-based criteria such as the PaO₂/FiO₂ ratio are difficult to interpret in fenestrated Fontan or Glenn circulation, and strict fulfilment of ARDS criteria cannot be assumed in this physiology. ^{Reference Blondonnet, Constantin, Sapin and Jabaudon6}

Interstitial pneumonia was considered unlikely because paediatric interstitial pneumonia typically presents with chronic or fibrotic patterns. ^{Reference Marczak, Krenke and Griese7} Although interstitial biomarkers were markedly elevated, such rises can occur in acute respiratory distress syndrome. Notably, KL-6 levels in our patients greatly exceeded those previously reported in paediatric ARDS or respiratory complications, including ∼956 ± 400 U/mL in ARDS/sepsis/traumatic brain injury ^{Reference Briassoulis, Mavrikiou and Margeli8} and ∼316 ± 39 U/mL in severely disabled children. ^{Reference Ochi, Fukuda and Ohmori9}

These findings support the interpretation that these cases represent severe paediatric acute respiratory distress syndrome with unusually high epithelial-injury biomarkers rather than primary interstitial lung disease.

Clinical implications and future directions

These cases highlight that Glenn/Fontan physiology may amplify lung injury once inflammation or infection occurs. Managing haemodynamics alone may be insufficient; early recognition of inflammatory triggers and consideration of biomarker monitoring could help identify patients at risk of prolonged recovery. Approaches that support endothelial integrity, lymphatic drainage, or modulation of inflammation may also be beneficial.

In Case 3, KL-6 decreased after conversion from non-pulsatile to pulsatile flow with a BT shunt, suggesting that restoring pulsatility may aid alveolar recovery. Future studies should include larger Glenn/Fontan cohorts with serial biomarker tracking, advanced imaging, and molecular profiling to identify susceptibility factors and guide precision strategies for preserving pulmonary function in single-ventricle palliation. ^{Reference Kawamura, Yamakuchi, Ueno, Hashiguchi and Okamoto2,Reference Tsujioka, Nishimura and Nishi10}